{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:13:55Z","timestamp":1783577635059,"version":"3.55.0"},"reference-count":116,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Tay-Sachs and Allied Diseases Association (NTSAD), Boston, MA 02135, USA","award":["NTSAD_DMUMG1"],"award-info":[{"award-number":["NTSAD_DMUMG1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Biomarkers currently available for the diagnosis, prognosis, and therapeutic monitoring of GM1 gangliosidosis type 2 (GM1T2) disease are mainly limited to those discovered in targeted proteomic-based studies. In order to identify and establish new, predominantly low-molecular-mass biomarkers for this disorder, we employed an untargeted, multi-analyte approach involving high-resolution 1H NMR analysis coupled to a range of multivariate analysis and computational intelligence technique (CIT) strategies to explore biomolecular distinctions between blood plasma samples collected from GM1T2 and healthy control (HC) participants (n = 10 and 28, respectively). The relationship of these differences to metabolic mechanisms underlying the pathogenesis of GM1T2 disorder was also investigated. 1H NMR-linked metabolomics analyses revealed significant GM1T2-mediated dysregulations in \u226513 blood plasma metabolites (corrected p &lt; 0.04), and these included significant upregulations in 7 amino acids, and downregulations in lipoprotein-associated triacylglycerols and alanine. Indeed, results acquired demonstrated a profound distinctiveness between the GM1T2 and HC profiles. Additionally, employment of a genome-scale network model of human metabolism provided evidence that perturbations to propanoate, ethanol, amino-sugar, aspartate, seleno-amino acid, glutathione and alanine metabolism, fatty acid biosynthesis, and most especially branched-chain amino acid degradation (p = 10\u221212\u221210\u22125) were the most important topologically-highlighted dysregulated pathways contributing towards GM1T2 disease pathology. Quantitative metabolite set enrichment analysis revealed that pathological locations associated with these dysfunctions were in the order fibroblasts &gt; Golgi apparatus &gt; mitochondria &gt; spleen \u2248 skeletal muscle \u2248 muscle in general. In conclusion, results acquired demonstrated marked metabolic imbalances and alterations to energy demand, which are consistent with GM1T2 disease pathogenesis mechanisms.<\/jats:p>","DOI":"10.3390\/cells10030572","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T11:46:09Z","timestamp":1614944769000},"page":"572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Rapid Identification of New Biomarkers for the Classification of GM1 Type 2 Gangliosidosis Using an Unbiased 1H NMR-Linked Metabolomics Strategy"],"prefix":"10.3390","volume":"10","author":[{"given":"Benita C.","family":"Percival","sequence":"first","affiliation":[{"name":"Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne L.","family":"Latour","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN 37232-0252, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia J.","family":"Tifft","sequence":"additional","affiliation":[{"name":"Deputy Clinical Director, National Human Genome Research Institute, Director, National Institutes of Health, Bethesda, MD 20892-1205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1502-3734","authenticated-orcid":false,"given":"Martin","family":"Grootveld","sequence":"additional","affiliation":[{"name":"Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.ymgme.2008.04.012","article-title":"GM1 gangliosidosis: Review of clinical, molecular, and therapeutic aspects","volume":"94","author":"Scaglia","year":"2008","journal-title":"Mol. 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